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Sequential actions of EOMES and T-BET promote stepwise maturation of natural killer cells

Abstract : EOMES and T-BET are related T-box transcription factors that control natural killer (NK) cell development. Here we demonstrate that EOMES and T-BET regulate largely distinct gene sets during this process. EOMES is dominantly expressed in immature NK cells and drives early lineage specification by inducing hallmark receptors and functions. By contrast, T-BET is dominant in mature NK cells, where it induces responsiveness to IL-12 and represses the cell cycle, likely through transcriptional repressors. Regardless, many genes with distinct functions are co-regulated by the two transcription factors. By generating two gene-modified mice facilitating chromatin immunoprecipitation of endogenous EOMES and T-BET, we show a strong overlap in their DNA binding targets, as well as extensive epigenetic changes during NK cell differentiation. Our data thus suggest that EOMES and T-BET may distinctly govern, via differential expression and co-factors recruitment, NK cell maturation by inserting partially overlapping epigenetic regulations.
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https://hal.archives-ouvertes.fr/hal-03357265
Contributor : Pierre-Olivier Vidalain Connect in order to contact the contributor
Submitted on : Tuesday, September 28, 2021 - 5:20:49 PM
Last modification on : Friday, October 29, 2021 - 8:18:07 AM

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Jiang Zhang, Stéphanie Le Gras, Kevin Pouxvielh, Fabrice Faure, Lucie Fallone, et al.. Sequential actions of EOMES and T-BET promote stepwise maturation of natural killer cells. Nature Communications, Nature Publishing Group, 2021, 12 (1), ⟨10.1038/s41467-021-25758-2⟩. ⟨hal-03357265⟩

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